CYP21 Genotype, Adult Height, and Pubertal Development in 55 Patients Treated for 21-Hydroxylase Deficiency

Abstract

In a retrospective study we evaluated long-term growth, pubertal developmental patterns to final height (FH), and medication in 55 patients (35 females) affected by 21-hydroxylase deficiency. The patients were classified into 3 groups according to predicted mutation severity: group A (11 women and 9 men), homozygous or compound heterozygous for null or In2 splice mutations [residual enzymatic activity (RA), <1%]; group B (11 women and 4 men), homozygous for I172N or R341P or R426H mutations (RA, approximately 2-3%) or compound heterozygous with any of the group A or B mutations; and group C (13 women and 7 men), homozygous for P30L or V281L or P453S mutations (RA, >30%) or compound heterozygous with any of the group A, B, or C mutations. Three patients showed unclassifiable genotypes. FH was similar in the female groups, whereas male patients in group B were shorter than males in groups A and C. Fifty-five percent of patients in group A, 33% in group B, and 40% in group C reached an FH within 0.5 SD of target height. Four of the 7 patients diagnosed via neonatal screening achieved an FH equal to or above the target height. In the entire group, early diagnosis (<1 yr) improved height outcome. Early diagnosed CAH patients who received lower cortisol equivalent doses during the first year of life reached a better FH. Our results underline the importance of mineralocorticoid therapy, as CAH subjects in groups A and B who did not receive this treatment showed reduced FH. Early diagnosis, the use of more physiological cortisol equivalent dosages during the first year of life, and the extension of mineralocorticoid therapy to all classical patients are shown to improve the auxological outcome. Genotypic analysis helped to interpret the height results of our cases and prospectively may represent a useful tool for improving the therapeutic choice and the height outcome.

Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency.

“…We noted low final height compared with target height, consistent with former publications (25)(26)(27)(28), while the onset of pubertal height was normal. Height gain was also reported as poor during pubertal years in studies conducted by Stikkelbroeck et al (29) and van der Kamp et al (30).…”

Final height in congenital adrenal hyperplasia: the dilemma of hypercortisolism versus hyperandrogenism

“…who showed a positive correlation of FHZ and height at 2 years of age in salt-losing patients (21), the present study corroborates that height loss occurs mainly within the first two years of life. In addition, some reports showed that FH was greater in patients with early treatment, up to 20 months (24) and before 3 years of CA (20), although these data are controversial among the authors (3,23). In this study, a group of patients who initiated treatment early reached their TH.…”

“…Studies evaluating GC effect during childhood evidenced a negative influence of the daily dose of GC upon growth velocity and FH in children up to one or two years of CA and in prepubertal children (11,(20)(21)(22)(23). Similar to Manoli and cols.…”

21-Hydroxylase Genotyping in Australasian Patients with Congenital Adrenal Hyperplasia

“…The members of this family with NC CAH (father, sister) were only detected as a consequence of the presentation of the proband with SW CAH. The father had early puberty and diminished adult height which has been reported in NC CAH 40 " 44 .…”